This research project is based on the concept that lamina I of the dorsal horn is an integral component of the central representation of pain and temperature sensibility. Only lamina I receives small-diameter primary afferent input from all tissues of the body and contains a specific concentration of nociceptive and thermoreceptive neurons. Lamina I neurons form half of the spinothalamic tract (STT), and their ascending axons are concentrated in the critical location for pain and temperature sensation. The functional and anatomical organization of lamina I projections needs to be elucidated. In the preceding grant period, we identified with anatomical, immunohistochemical and physiological methods a specific lamina I STT thalamic relay nucleus (VMpo) for pain and temperature sensation in macaques and humans, and we demonstrated lamina I propriospinal and brainstem projections that could provide the basis for noxious and thermal somato-autonomic reflexes. In cats, we also identified three major physiological/morphological classes of lamina I STT cells, showed that they have selective thalamic projections, and demonstrated that a simple model of thalamo-cortical integration of the activity of these lamina I STT sensory channels can explain the thermal grill illusion and the burn of cold pain. The proposed experiments address the functional anatomy of the lamina I spino-thalamo-cortical pathway in primates. We will (i) determine whether the cortical projections of the major lamina I STT projection targets that we have identified (VMpo, VPI, and MDvc) in the monkey correspond with the major cortical areas activated by pain in human PET studies, (2) determine whether the different morphological classes of lamina I STT neurons identified in the cat are distinguishable in the monkey and project differentially, (3) examine whether VMpo and neighboring structures in monkey and human thalamus are chemoarchitectonically organized, (4) quantitatively determine whether physiologically distinct classes of lamina I STT cells exist in the monkey like those identified in the cat, and (5) quantitatively determine whether VMpo neurons maintain the physiological specificity of lamina I response classes or show evidence of integrative convergence of lamina I STT inputs. The thermal grill and the itch-inducing agent histamine will also be used to examine whether the postulated integration of lamina I STT activity occurs in VMpo. These experiments test specific hypotheses that delineate integral components of the central substrates of specific pain and temperature sensibility in monkeys and humans. We believe that the postulated model of thalamo-cortical integration of lamina I sensory channels could provide a basis for the cold allodynia and burning dysesthetic pain that characterize the classic (central post-stroke) thalamic pain syndrome.